reductive amination

Reductive amination is a two-in-one move that builds a new carbon–nitrogen bond by first letting an amine and a carbonyl compound (an aldehyde or ketone) condense, then locking the result in place with a reducing agent. It is one of the gentlest and most general ways to attach an alkyl group to a nitrogen, and like amide coupling it shows up constantly in medicinal chemistry.

When an amine meets an aldehyde or ketone, they reversibly join and lose water to form an imine or iminium ion. On its own that intermediate is fragile, so a mild hydride reagent such as sodium triacetoxyborohydride or sodium cyanoborohydride reduces it to a stable amine. The mildness matters: these reagents preferentially reduce the iminium over the starting carbonyl, letting the reaction proceed in one pot without over-reduction.

Reductive amination is prized because it is reliable, tolerant of many functional groups, and pairs beautifully with parallel synthesis since amines and carbonyls are both abundant as building blocks. The honest caveats are that it adds a secondary or tertiary amine (which can raise basicity and affect properties), it can over-alkylate to give unwanted bis-addition, and sterically hindered ketones may react sluggishly.